ORIGINAL ARTICLE
Alcohol at bedtime induces minor changes in sleep stages
and blood gases in stable chronic obstructive pulmonary disease
Nils Henrik Holmedahl&Britt Øverland&Ove Fondenes&
Ivar Ellingsen&Jon Andrew Hardie
Received: 26 February 2014 / Revised: 19 May 2014 / Accepted: 3 June 2014
#The Author(s) 2014. This article is published with open access at Springerlink.com
Abstract
Purpose/backgroundThe purpose of this study is to explore the effect of a moderate dose of alcohol on sleep architecture and respiration in chronic obstructive pulmonary disease (COPD). Alcohol depresses both hypercapnic and hypoxic ventilatory drives in awake, normal individuals and reduces the amount of rapid eye movement (REM) sleep and oxygen saturation (SpO2) in sleeping COPD subjects.
Methods Prospectively designed, open-label interventional study in a pulmonary rehabilitation hospital. Twenty-six (nine males) stable inpatients, median forced expiratory volume first second (FEV1) 40.5 % of predicted, median age 65 years, investigated by polysomnography including transcutaneous measurement of carbon dioxide pressure increase (ΔPtcCO2) in randomized order of either control sleep or intervention with 0.5 g of ethanol/kilogram bodyweight, taken orally im- mediately before lights off.
ResultsAlcohol induced a mean increase (95 % confidence interval, [CI]) in the meanΔPtcCO2of 0.10 kPa (0.002–0.206,
P=0.047) and a mean decrease (CI) in the REM-sleep percentage of total sleep time (REM % of TST) of 3.1 % (0.2–6.0), (P= 0.020). Six subjects with apnea/
hypopnea index (AHI)≥15 hadfewerapneas/hypopneas dur- ing alcohol versus control sleep (mean reduction of AHI 11 (1–20),P=0.046). Alcohol-sleep changes in SpO2, but not in ΔPtcCO2, correlated with daytime arterial pressures of carbon dioxide (PaCO2) and oxygen (PaO2).
Conclusion Occasional use of a moderate, bedtime dose of alcohol has only minor respiratory depressant effects on the majority of COPD subjects, and in a minority even slightly improves respiration during sleep. However, caution is appro- priate as this study is small and higher doses of alcohol may result in major respiratory depressive and additional negative health effects.
Keywords Ethanol . Transcutaneous blood gas monitoring . Hypoventilation . COPD . Carbon dioxide .
Polysomnography
Introduction
Chronic obstructive pulmonary disease (COPD) has a signif- icant morbidity and mortality [1], and chronic hypercapnic respiratory failure (CHRF) in COPD is associated with poor prognosis [2,3]. Heavy alcohol consumption has been shown to increase the risk of developing COPD [4–6]; on the other hand, mild alcohol intake may reduce the risk both of devel- oping severe pulmonary function abnormalities and of dying from COPD [7,8]. Sleep is characterized by periods of unsta- ble respiration, and in normal, awake individuals, hypoxic and hypercapnic ventilatory drives are depressed by alcohol [9].
Sleep hypoventilation (SH) has previously been shown to be frequent in severe COPD with CHRF and long-term oxygen therapy (LTOT) [10–12], and recently, we also found SH in Presentation at a conference: This material has not been presented at any
conference.
Clinical trial registration number: NCT00888342 N. H. Holmedahl (*)
:
I. EllingsenLHL-klinikkene, Glittre, Glittreklinikken, postboks 104 Åneby, 1485 Hakadal, Norway
e-mail: [email protected] B. Øverland
ENT-Department, Lovisenberg Diakonale Hospital, Oslo, Norway O. Fondenes
Norwegian National Centre of Excellence in Home Mechanical Ventilation, Haukeland University Hospital, Bergen, Norway N. H. Holmedahl
:
J. A. HardieDepartment of Clinical Science, University of Bergen, Bergen, Norway
DOI 10.1007/s11325-014-1020-y
some normocapnic, non-LTOT individuals with stable COPD [12]. Both in a study of 20 asymptomatic men aged 20 to 65 years [13] and in a study of 20 COPD subjects (19 men) [14], alcohol increased the number of sleep apneas. However, a study of 18 asymptomatic, postmenopausal women found no difference between placebo- and alcohol-influenced sleep in the number of episodes of apnea or hypopnea or in the frequency, length, or severity of oxygen desaturation [15]. In two small studies of four normal individuals and five subjects with stable COPD, alcohol taken immediately before sleep resulted in a moderately reduced mean SpO2and a reduced amount of rapid eye movement (REM) sleep [16,17]. To our knowledge, no studies have explored alcohol-induced chang- es in carbon dioxide pressure (PCO2) with polysomnography (PSG) in sleeping COPD patients. Concern is thus raised whether it is safe for individuals with COPD, especially those with CHRF or frequent apneas/hypopneas, to occasionally consume alcohol before sleep.
Hypothesizing an increase in the PCO2 during sleep, the primary aim of this study was to explore to what extent a moderate dose of alcohol prior to sleep induces hypoventilation in stable COPD patients, secondary whether apneas/hypopneas and sleep architecture is al- tered, and finally whether the alcohol-induced changes in blood gases during sleep is correlated to daytime COPD characteristics.
Material and methods
Subjects
Study participants were a randomized selection from the 166 subjects described in a previous article [12], all Caucasians with GOLD [18] defined COPD and inpatients at the Glittreklinikken Pulmonary Rehabilitation Hospital included from January 2010 through June 2011. The following exclu- sion criteria were used: diagnosed obstructive sleep apnea (OSA); COPD exacerbation within 3 weeks prior; other seri- ous lung comorbidity (i.e., cancer, sarcoidosis, restrictive lung disease) or diseases affecting thoracic or abdominal move- ment, unstable angina pectoris, hypertension, diabetes mellitus, myocardial infarction within last 3 months, cerebral infarction, and addiction to drugs, alcohol, or narcotics. At inclusion, study subjects were randomized to receive alcohol, 5 mg of Zopiclone (a sleep drug), or supplementary oxygen (data from the latter two interventions not yet published). All subjects used prescribed medication, but no drugs known to be respiratory depressants were taken from 48 h prior to first PSG recording until end of study. The protocol was approved by the Regional Ethics Committee in south-eastern Norway.
As shown in Fig.1, 26 pairs of PSG from control and alcohol- influenced sleep were analyzed.
Measurements
All subjects slept in their own bed at the hospital with full PSG for three nights; first night for acquaintance with the equip- ment, second and third nights randomized to either control or alcohol-influenced sleep. PSG was recorded online from Embla A101with transcutaneously measured carbon dioxide pressure (PtcCO2) from Tosca 5002 to a bedside computer using Somnologica Studio Version 3.3 software. Channel setup was according to the 2007 recommendations from the American Academy of Sleep Medicine (AASM) [19]. PSGs were recorded only during weekdays. Alcohol 0.5 mg per kg bodyweight (corresponding to about three glasses of wine in a 70-kg person) was given as 96 vol% ethanol diluted in 200 ml of orange juice and ingested the last 30 min prior to sleep [20].
Immediately before lights off, breath analysis by Lion alcometer 5003was used to check that study-alcohol was taken.
Unpublished data collected at Glittreklinikken prior to the study showed equivalence between changes in PtcCO2
and PaCO2, but a delay time of 54–57 s. Details regarding delay time, PtcCO2signal stabilization, sampling frequency, and calculations according to sleep stages are given in our previous article [12].
Fig. 1 Inclusion
1Medcare Flaga, Reykjavik, Iceland.
2Radiometer, Basel, Switzerland.
3Lion Laboratories Ltd., Vale of Glamorgan, UK.
Arterial blood gas samples4were collected after a 10-min seated rest at approximately 2 p.m. prior to each PSG record- ing and analyzed within 10 min on the Radiometer ABL720Flex.5At sampling, all subjects were breathing room air, with an exception for those on LTOT who used their prescribed dose of supplementary oxygen. Height, weight, and lung function tests including postbronchodilator spirom- etry, diffusing capacity (DLCO), and body plesmography of total lung volumes were recorded on MasterScreen Pneumo6 as previously described [12], reference values are based on equations from the European Community for Coal and Steel [21].
S l e e p s c o r i n g w a s d o n e b y t w o e x p e r i e n c e d polysomnographists according to recommendations from the AASM [12,19]; a hypopnea was scored when nasal pressure dropped≥30 % for≥10 s with≥4 % desaturation drop from baseline, with≥90 % of the event’s duration meeting the amplitude reduction criteria for hypopnea (criterion A).
Sleep hypoventilation is defined by the AASM as an increase of 1.3 kPa or more in PaCO2during sleep, to a value exceed- ing 6.7 kPa for at least 10 min [22].
Statistical analysis
Sample size calculations up front showed that for N=28, a PtcCO2difference between alcohol and control sleep would be detected with 80 % probability at a two-sided 0.05 signifi- cance level if the true difference was 0.25 kPa, assuming a within-patient standard deviation of 0.32 kPa7
Data were assessed for normality of distribution and ho- mogeneity of variance. No violation of the assumptions of normality, linearity, multicolinearity, and homoscedasticity was found preliminary to regression analysis.
Differences between groups with continuous, paired para- metric data were analyzed with Student T, paired non- parametric data with Wilcoxon signed rank, independent non-parametric data with Mann-Whitney U, and non- parametric data in more than two groups by Kruskal-Wallis tests. Paired proportions were analyzed with McNemar chi- square test (P value uncorrected) and correlations with Pearson’sr.
Two-sidedPvalues of≤0.05 were considered significant in testing the main hypothesis, whereas a significance level of P≤0.025 was applied in the remaining analyses. All analyses were performed using IBM SPSS Statistics version 19.
Results
The 9 men and 17 female (Table1) were on average hyper- inflated with impaired gas exchange and severe airway ob- struction, 14 (54 %) of the 26 subjects at GOLD stages III and IV. Four subjects (16 %) had daytime hypoxemia (arterial pressures of oxygen (PaO2)<8.0 kPa), whereas only one had PaO2>12.0 kPa. CHRF (PaCO2≥6.3 kPa) was found in four subjects, of which three used LTOT. The study group had a normal median BMI, five subjects (19 %) being underweight (BMI<21), whereas five were obese (BMI≥30).
As indicated in Table 2, alcohol at bedtime reduced the REM-sleep percentage of total sleep time (REM % of TST) with a mean (SD) of 3 (7) %, and the number of awakenings with 8 (13). However, eight subjects had anincreasedamount of REM sleep when influenced by alcohol (Fig.2, groups 2 and 4).
The mean PtcCO2increase from supine, resting value prior to sleep (ΔPtcCO2) was higher during alcohol versus control sleep (a mean (SD) increase of 0.10 (0.25) kPa), despite nine subjects having a decrease in the mean ΔPtcCO2 (Fig. 2, groups 3 and 4). As shown in Table4, alcohol-sleep changes in meanΔPtcCO2and mean SpO2did not correlate.
Sleep hypoventilation (SH) as defined by the AASM was found in two subjects (8 %) during control sleep and in five subjects (19 %) in alcohol sleep [22]; however, the difference was not statistically significant as one subject with SH in control sleep had no SH during alcohol sleep.
Ten subjects had a drop in alcohol-sleep mean SpO2 of
>1 %, whereas the NREM sleep mean SpO2for the whole study group decreased with a mean (SD) of 0.9 (2.1) % (P=.019). No significant change was found in REM sleep (Table 2). Interestingly, Table 2 also shows no respiratory depressant effect of alcohol during the awake periods after the initial sleep onset (N0) nor was there significant N0 changes in meanΔPtcCO2and mean SpO2when analyzing only subjects with alcohol increased sleep mean ΔPtcCO2
(groups 1 and 2, Fig.2).
The median values of apneas/hypopneas and desaturations per hour of sleep (AHI and ODI, respectively) were not changed by alcohol. Despite the exclusion of diagnosed OSA prior to the study, six subjects (four males) had an AHI of≥15 per hour in control sleep. Intriguingly, Table3indicates that this subgroup had alcohol sleepdecreasesin median AHI and ODI, all with increased mean ΔPtcCO2and decreased REM % of TST.
As the three LTOT users were outliers in the data distribu- tion of the mean SpO2change, partial correlation was applied, controlling for LTOT use (yes/no). Alcohol-sleep changes in the mean SpO2(ΔASSpO2) were highly correlated to daytime PaO2and inversely to PaCO2(Table4). However, this was not the case regarding the alcohol-sleep changes in the mean ΔPtcCO2nor did hypoventilation during alcohol sleep corre- late to spirometry or demographic data.
4PICO50, Radiometer, Copenhagen, Denmark.
5Radiometer, Copenhagen, Denmark.
6Jaeger-Toennies, Hoechberg, Germany.
7In our previous study of 100 COPD subjects [12], the mean increase (standard deviation) in PtcCO2during spontaneous sleep was 0.49 (0.32) kPa.
Finally, hierarchical multiple regressions were performed to determine whether theΔASSpO2could be explained by day- time COPD characteristics. PaO2and PaCO2were entered at step 1, explaining 34 % of the variance inΔASSpO2. After the entry of LTOT (yes/no) at step 2, the total variance explained by the model was 49 %, (F(3, 22)=7.09,P=0.002). Thus, LTOT (yes/no) explained an additional 15 % of the variance in the ΔASSpO2 after controlling for PaO2 and PaCO2 (R2 change=0.015,Fchange (1, 22)=6.48,P=0.018). In the full model, using LTOT recorded the highest beta value (0.70, P<.018), over PaCO2 (−0.59, P<0.031), whereas PaO2 did not make a unique contribution (0.31,P=0.116).
Table 2 Control versus alcohol-influenced sleep
N=26 Control sleep
Median (IQR)
Alcohol sleep Median (IQR)
Pvalue
Sleep architecture
TST, min 354.0 (65.3) 354.0 (62.5) 0.501
REM % of TST 25 (8) 20 (9) 0.020
NREM % of TST 75 (8) 80 (9) 0.020
WASO, min 45.7 (74.7) 40.9 (48.5) 0.361
Awakenings 28 (18) 19 (17) 0.012
AI 15.5 (10.0) 18.6 (10.0) 0.920
Ventilation
AHI 9.7 (10.2) 10.4 (16.4) 0.517
HI 4.8 (6.2) 6.3 (8.6) 0.309
ODIa 5.5 (11.6) 8.3 (12.8) 0.548
Mean SpO2%
N0 94.0 (5.1) 93.9 (5.6) 0.551
NREM 93.7 (4.6) 93.2 (5.4) 0.019
REM 92.5 (5.4) 92.8 (6.4) 0.258
Sleep 93.4 (4.7) 93.2 (5.7) 0.058
MeanΔPtcCO2kPa
N0 0.19 (0.23) 0.15 (0.22) 0.638
NREM 0.39 (0.34) 0.55 (0.36) 0.035
REM 0.67 (0.46) 0.67 (0.42) 0.082
Sleep 0.49 (0.35) 0.58 (0.36) 0.047
Sleep hypoventilation
SHb 8 (27) 19 (40) 0.179
TSTtotal sleep time,REMrapid eye movement sleep,NREMnon-REM sleep,WASOwake after sleep onset,Awakeningsnumber of awakenings after sleep onset,AInumber of arousals per hour (arousal index),AHI number of apneas/hypopneas per hour (apnea/hypopnea index),HInum- ber of hypopneas per hour (hypopnea index),ODInumber of oxygen desaturations per hour (oxygen desaturation index),SpO2oxyhemoglobin saturation by pulse oximetry,N0 awake after initial sleep onset,Sleep=
NREM + REM,ΔPtcCO2carbon dioxide pressure increase from supine, resting value prior to sleep,SH sleep hypoventilation defined by the American Academy of Sleep Medicine as an increase of 1.3 kPa or more in PaCO2during sleep, to a value exceeding 6.7 kPa for at least 10 min
aN=25, one missing because of defect finger probe
bPercent of“Yes”within group (SD), instead of median (IQR)s Table 1 Study population
N=26 Median (IQR) Demographic data
Gender female 17 (65)a
Age, years 65.5 (14.0)
BMI, kg/m2 25.0 (6.5)
Smoking habit
Pack years 30.4 (22.4)
Current smoker 4 (15)a
Medication
LTOT 3 (12)a
SABA/LABA 24 (92)a
Statin 4 (15)a
ACE/AII 3 (12)a
Thiazide 3 (12)a
ASA 3 (12)a
Spirometry
FVC, % of pred 81.0 (35.3)
FEV1, % pred 40.5 (30.3)
FEV1/FVC, ratio 0.46 (0.21)
DLCO1, mmol/min/kPa 3.92 (2.49)
RV/TLC2, ratio 0.56 (0.20)
Clinical data
CAT, score 18 (7)
MMRC, score 2.0 (1.0)
6-MWD3, meter 420 (205)
BODE index 2.0 (4.0)
Laboratory data
PaO2, kPa 9.66 (1.98)
PaCO2, kPa 5.07 (.96)
SaO2, % 96.2 (3.3)
Alcohol, ppt 0.81 (0.64)
IQRinter quartile range,BMIbody mass index,LTOTlong-term oxygen therapy,SABA/LABAshort- and/or long-acting beta-2 receptor agonist, ACE/AIIangiotensin converting enzyme and/or angiotensin II antagonist, Thiazidehydrochlorothiazide,ASAacetylic salicylic acid,FVC % of pred forced vital capacity as percent of predicted value,FEV1% of predforced expiratory volume first second as percent of predicted value,DLCO diffusing capacity of the lung for carbon monoxide,RVresidual volume, TLCtotal lung capacity,CATCOPD assessment test,MMRCmodified medical research council questionnaire, 6-MWD6 min walking distance, BODEBMI/obstruction/dyspnea/exercise capacity,PaO2arterial pressure of oxygen,PaCO2arterial pressure of carbon dioxide, SaO2 arterial oxygen saturation,.Alcoholparts per thousand measured by breath anal- ysis immediately prior to sleep
aN(% of study subjects), instead of median (IQR)
1N=22, four missing from DLCO because of insufficient vital capacity or because they could not hold their breath for 10 s
2N= 24, two missing from body plethysmography because of claustrophobia
3N=25, one missing from 6-MWD, reason unknown
Discussion
When stable COPD subjects (2/3 female) are given a moderate dose of alcohol immediately prior to sleep, we find a very modest sleep hypoventilation as a group mean increase in PtcCO2of about 0.1 kPa and a decrease in SpO2of less than 1 %. This hypoventilation is not detectable when subjects are awake after the initial sleep onset. The mean REM % of TST is decreased in alcohol sleep. A novel finding is subgroups showing opposite characteristics as slight hyperventilation with decreased amount of REM sleep and hypoventilation with increased REM percentage of TST. AHI and ODI are not significantly increased by alcohol; however, in overlap subjects (AHI≥15/h), AHI and ODI are lower. Alcohol-sleep change in SpO2, but not PtcCO2, is associated to daytime blood gases, and a model with LTOT, PaCO2, and PaO2can explain about half of the variation in alcohol sleep change in SpO2.
In a much referred study from 1967, Yules et al. gave 1 g of ethanol/kg body weight to four male graduate students 4 h prior to sleep and found that the REM-sleep time reduced as a mean for the group; however, one subject showed no change in REM-sleep time [16]. Later, Easton et al. gave five COPD subjects 0.78 g of alcohol/kg bodyweight immediately prior to sleep and found a mean TST decrease of 19 %, a REM-sleep percentage of TST decrease by 12 % and a mean drop in SpO2
of about 3 % [17]. In 2007, Brander et al. studied nine males with advanced COPD using 0.5 g of alcohol/kg bodyweight albeit taken earlier in the evening, they did not record PSG but found only a trivial decrease in SpO2(<1 %) during the first 2 h of the reported sleep [23].
In the present study, we find REM % of TST decreased as in the studies referred above, however, only in 18 (69 %) of the subjects. One possible explanation for the eight subjects showingincreasedREM % of TST can be alcohol abstinence.
Easton et al. found the REM % of TST gradually increasing when giving alcohol repeatedly for several nights. Although none of our study subjects had a drinking problem (otherwise they would not have been included), some could nevertheless have used alcohol regularly before admission, and thus the abstinent state during the first week at the hospital might explain the increase in REM sleep when given alcohol.
However, we find it unlikely that as many as 31 % of the study subjects had an undisclosed alcohol problem, and as Yules et al. also described one subject with no change in REM-sleep time [16], hitherto unknown effects of alcohol on sleep can have caused the increased mean REM % of TST in some of the subjects in the present study (Fig.2).
In a previous article, we showed thatΔPtcCO2increases with depth of NREM sleep in stable COPD and with the highest values recorded during REM sleep [12]. Thus, finding the REM percentage of TST beingreducedin alcohol sleep, one would expect to find the meanΔPtcCO2to bedecreased.
Indeed, although not clinically impressive, the seven (27 %) Fig. 2 Alcohol-induced changes in meanΔPtcCO2versus changes in
REM-sleep percentage of TST. Each subject (N=26) is represented by a colored figure according to group (legend in panel). Mean PtcCO2in group 1 (median (IQR) 0.26 (0.28) kPa) differed significantly from group 3 (−0.20 (0.23) kPa,P<0.0005), but not from group 2 (0.11(0.10) kPa, P=0.027). The change in REM percentage of TST was significantly different between groups 1 and 2 (median (IQR)=−4.5 (6.9) % versus 3.9 (8.9) %,P=0.001).Change in meanΔPtcCO2is the difference in the mean increase in transcutaneous carbon dioxide pressure between alcohol and control sleep.Change in mean REM % of TSTis the difference in the mean rapid eye movement sleep percent of total sleep time between alcohol and control sleep
Table 3 Alcohol-induced sleep changes in overlap subjects N=6 (four male) Control sleep
Median (IQR)
Alcohol sleep Median (IQR)
Pvalue
REM % of TST 25 (12) 21 (15) 0.028
NREM meanΔPtcCO2, kPa 0.48 (0.39) 0.68 (0.27) 0.028 REM meanΔPtcCO2, kPa 0.64 (0.63) 0.91 (0.35) 0.028 Sleep meanΔPtcCO2, kPa 0.51 (0.46) 0.75 (0.28) 0.028 Sleep mean SpO2, % 93.3 (3.8) 93.2 (6.5) 0.075
ODI 32 (28) 24 (22) 0.028
AHI 39 (40) 26 (22) 0.046
REM AHI 49 (43) 36 (28) 0.075
NREM AHI 31 (46) 30 (23) 0.116
As no record of daytime sleepiness was available, overlap was defined as having at least 15 apneas/hypopneas per hour of sleep in subjects with chronic obstructive pulmonary disease
NREM meanΔPtcCO2mean pressure of transcutaneous carbon dioxide in non-rapid eye movement sleep,REM meanΔPtcCO2mean pressure of transcutaneous carbon dioxide in rapid eye movement sleep,Sleep mean ΔPtcCO2mean pressure of transcutaneous carbon dioxide in REM and NREM sleep,Sleep mean SpO2mean oxyhemoglobin saturation during sleep measured by pulse oximetry,REM % of TSTREM-sleep percentage of total sleep time,AHInumber of apneas/hypopneas per hour of sleep, REM AHIAHI during REM sleep,NREM AHIAHI during NREM sleep
subjects in group 3 in Fig.2fit in this picture. Brief alcohol exposure is moderately bronco-dilating and increases the mucociliary motility in asthmatics [24], and thus can relieve nocturnal wheezing in reversible COPD subjects, and possibly improve gas exchange in the lungs. However, the 11 (42 %) subjects with reduced REM % of TST andincreasedPtcCO2
(group 1, Fig.2) are more in accordance with previous find- ings in COPD [17]. The hypoventilation demonstrated in the present study with only two subjects (8 %) having a mean alcohol-sleep increase inΔPtcCO2>0.5 kPa and less than half having a drop in mean SpO2>1 % was considerably less impressive than Easton et al.’s findings and more in line with the results of Brander et al.[17,23]. One obvious explanation
is the amount of alcohol and the time of ingestion related to sleep onset, as Brander et al. gave less alcohol earlier in the evening compared to Easton et al., the present study using same amount of alcohol as Brander et al., but given immedi- ately before lights off. Thus, as REM sleep is more frequent the second half of the night when most of the alcohol is metabolized, REM-sleep hypoventilation is not significantly changed. Another explanation can be the number of study subjects; as previous studies included only up to six subjects, they could have missed the individuals having decreased PtcCO2during alcohol sleep.
Previous studies have shown increased numbers of apneas in alcohol-sleep in asymptomatic and in snoring males, in mild to moderate OSA-males and in male, but not in female COPD subjects [13,25,26,14,15]. The present study did not find AHI, HI, and ODI significantly increased by alcohol.
This can partly be explained by the majority of female subjects in the present study. Also, as apneas/hypopneas are most frequent in REM sleep, occurring at low alcohol content, the reduced REM % of TST in alcohol-sleep can result in the total AHI being unchanged. However, the subgroup of mostly men with control sleep AHI≥15/h havingdecreasedAHI and ODI during alcohol sleep seems to contradict previous findings in males. All these individuals are hypoventilating, yet they have fewer apneas, and although not statistically significant, the REM-sleep AHI tends to be lower in alcohol-sleep. A reduced tidal volume with increased frequency of respiration, shorter episodes of REM-sleep, less mucus, and reduced bronchial constriction can be possible explanations.
Interestingly, no changes are found inΔPtcCO2or SpO2in N0 (awake after initial sleep onset), suggesting that moderate doses of alcohol has a significant effect on the central respiratory control only during sleep. This is in support of Sahn et al., who did not find significant alcohol-induced hypoventilation (neither as decreased PO2 nor increased PCO2) in six awake subjects with severe COPD after drinking 0.78 g of alcohol/kg bodyweight [27].
Having COPD with daytime respiratory failure correlates with alcohol-induced sleep hypoventilation, however, only as daytime blood gases versusΔASSpO2, and not hypoventilation as change in meanΔPtcCO2(Table4). As the multiple linear regressions with the variables LTOT, PaO2, and PaCO2can explain only half of the decrease in SpO2in alcohol sleep, advice to COPD patients regarding the use of alcohol cannot be based on whether they have respiratory failure or not. Nor is the severity of COPD according to FEV1 as percentage of predicted, the transfer factor for carbon monoxide (DLCO) or the residual volume as percentage of total lung volume (RV/
TLC) highly associated with the alcohol-induced sleep hypoventilation.
This study is to our knowledge the first to explore sleep hypoventilation as both oxygen desaturation and carbon diox- ide increase in moderately alcohol-intoxicated COPD Table 4 Correlation between alcohol-induced blood gas changes in sleep
and study population characteristics
N=26 Change in mean
SpO2a Change in mean ΔPtcCO2
Pearson’sr Pvalue Pearson’sr Pvalue Demographic data
Age, years −0.11 0.616 0.02 0.914
Gender 0.08 0.709 0.06 0.784
BMI kg/m2 −0.13 0.543 0.13 0.516
Laboratory data
PaO2, kPa 0.51 0.009 −0.25 0.227
PaCO2, kPa −0.58 0.002 0.11 0.604
pH 0.37 0.071 0.05 0.816
Spirometry
FVC % of pred 0.28 0.170 −0.04 0.855
FEV1 % of pred 0.32 0.125 −0.03 0.886
DLCO mmol/min/kPab 0.32 0.161 −0.23 0.308
RV/TLC ratioc −0.28 0.202 0.01 0.950
Sleep
Change in REM % of TST
0.12 0.554 −0.15 0.454
Change in awakenings −0.11 0.602 0.22 0.274
Change in mean SpO2 − − −0.30 0.135
Change in mean SpO2difference between alcohol and control sleep in the mean oxygen saturation,Change in meanΔPtcCO2difference between alcohol and control sleep in the mean increase from awake, supine, transcutaneous carbon dioxide pressure,BMIbody mass index,PaO2
arterial pressure of oxygen,PaCO2arterial pressure of carbon dioxide, FVC % of predforced vital capacity as percent of predicted value,FEV1%
of predforced expiratory volume first second as percent of predicted value,DLCOdiffusing capacity of the lung for carbon monoxide,RV residual volume,TLC total lung capacity,Change in REM % of TST difference in the mean rapid eye movement sleep percent of total sleep time between alcohol and control sleep,Change in awakeningsdifference in the number of awakenings between alcohol and control sleep
aPartial correlation controlling for LTOT use is tabulated
bFour missing from DLCO because of insufficient vital capacity or because they could not hold their breath for 10 s
cTwo missing from body plethysmography because of claustrophobia
subjects; however, it has some limitations. Many comparisons increase the risk of type 1 statistical errors (falsely rejecting the null hypothesis when in fact it is true) and although an alpha-correction was applied in interpreting the results of analyses other than the main hypothesis, the significance of the results must be viewed with this risk in mind. The open- label design can add a placebo bias to the alcohol intervention.
However, we find it less likely that ventilation during sleep is affected by the knowledge of being drunk, and the fact that blood gases were unchanged when awake after initial sleep onset indicates little placebo impact. Another limitation is the lack of a detailed, structured alcohol consumption interview, as regular alcohol ingestion, although not being considered as a drinking problem, can result in a very different sleep and breathing patterns as discussed above. Thirdly, no records were made of whether or not the study subjects were fasting at the time of alcohol ingestion. The alcohol breath test per- formed immediately before lights off was not considered a valid measurement of blood alcohol content (BAC) as such analyses are considered to be unreliable in COPD [28–30];
nevertheless, the breath analyses showed an unexpected high variability (Table1). Food taken together with alcohol can delay peak BAC, possibly explaining some of this variability.
If BAC correlates withΔPtcCO2, fasting individuals can have peak BACs and thus highΔPtcCO2, values early in the night, compared to those with their BAC peak well into the night.
However, supper at the hospital was at 6:30 p.m., and we find it unlikely that many study subjects ate at a later time.
Conclusion/summary
In this study of stable COPD patients drinking a moderate dose of alcohol immediately prior to lights off, we found a very modest sleep hypoventilation as increased mean ΔPtcCO2, a reduced REM % of TST, and no changes in AHI. However, this combination of hypoventilation and decreased REM-sleep time was evident in less than half of the subjects, as about one-fourth had a minor sleep hyperventilationwith reduced REM % of TST and another one-fourth was hypoventilating with anincreasein REM % of TST. Also, subjects with COPD and OSA (overlap) hadlower median AHI and ODI in alcohol-sleep versus control sleep.
We found an association between daytime blood gases and alcohol-sleep hypoventilation as decreased SpO2, but not in- creasedΔPtcCO2, and a regression model with the variables LTOT-use, PaO2, and PaCO2could explain 49 % of the vari- ation in alcohol sleep SpO2change. As the blood gas changes were minor, the clinical implication of this study is that a single, moderate, bedtime dose of alcohol seems to have only minor respiratory depressant effects on the majority of COPD subjects, and in a minority even slightly improves respiration during sleep. However, caution must be applied as the study is
small, and higher doses of alcohol may result in major respi- ratory depressive and additional negative health effects.
Acknowledgments Financial support was received from the Norwe- gian ExtraFoundation for Health and Rehabilitation, LHL’s Research fund, Glittreklinikken LHL helse as and the Norwegian national centre of excellence in home mechanical ventilation. Minor grants received from the Norwegian lung medicine society/Takeda Nycomed, Major Eckbo’s endowments and the University of Bergen. PSG hardware and software were provided by ResMed Norway.
Conflict of interests This is not an industry supported study.
Nils Henrik Holmedahl: Has received lecture honorarium from Glaxo Smith Kline and a grant from the Norwegian Lung Medicine Society/
Takeda Nycomed.
Britt Øverland: No conflict of interest.
Ove Fondenes: No conflict of interest.
Ivar Ellingsen: No conflict of interest.
Jon Andrew Hardie: No conflict of interest.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
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